A Population-Based Cohort Study Examining the Long-term Risk of Repeated Surgery in Non-Helicobacter pylori-Infected PPU Patients Who Underwent Simple Closure

  • Shih-Chi WuEmail author
  • William Tzu-Liang Chen
  • Chih-Hsin Muo
  • Chung Y. Hsu
Original Article



The management of perforated peptic ulcer (PPU) has shifted from vagotomy/drainage to simple closure, followed by postoperative proton pump inhibitors (PPIs) and Helicobacter pylori (HP) eradication. Few studies have focused on the long-term impacts of this trend shift. We hypothesize that simple closure with PPIs is sufficient and does not carry an elevated rate of repeated surgery in non-HP-infected PPU patients.


Hospitalized PPU patients who underwent simple closure or truncal vagotomy/pyloroplasty (TVP) in the National Health Insurance Research Database (NHIRD) from 2000 to 2008 were collected. The index date was defined as the date of ulcer admission. Patients who underwent other ulcer surgeries (e.g., gastrectomy, highly or selective vagotomy), who had a history of HP infection, or who were < 18 or > 100 years old were excluded. Additionally, the distributions of postoperative nonsteroidal anti-inflammatory drug (NSAID) and PPI use were calculated using the Longitudinal Health Insurance Database (LHID).


After exclusion, a total of 66,413 patients were enrolled. There were 7232 (10.9%) patients who underwent TVP and 59,181 (89.1%) patients who underwent simple closure. The incidences of repeated ulcer-associated surgery were 5.10 and 23.05 versus 5.11 and 15.77 per 1000 person-years in the TVP cohort vs. the simple closure cohort before and after propensity score matching, respectively. When adjusted for age, sex, comorbidity, and Charlson comorbidity index score, the TVP cohort had a 68% (HR) and 66% (sHR) decreased risk compared with the simple closure cohort before propensity score matching, with a 67% decreased risk after propensity score matching in Cox proportional subdistribution hazard analysis and a 66% decreased risk in Fine-Gray proportional subdistribution hazard analysis. The LHID analysis showed a lower rate of postoperative NSAID use and a higher rate of postoperative PPI use in simple closure patients.


Our findings suggest that in the Asian population, simple closure increases the risk of repeated ulcer-associated surgery in non-HP-infected PPU patients compared with TVP patients. However, further studies are warranted.


Perforated peptic ulcer Simple closure Vagotomy Recurrent perforation 



perforated peptic ulcer


proton pump inhibitors (PPIs)


helicobacter pylori


truncal vagotomy/pyloroplasty


National Health Insurance Research Databases


nonsteroidal anti-inflmmatory drugs


Longitudinal Health Insurance Database


Charlson comorbidity index


gastroesophageal reflux disease


International Classification of Diseases, Ninth Revision, Clinical Modification


acquired immune deficiency syndrome


confidence intervals


hazard ratio


subdistribution hazard ratio


body mass index


Author Contributions

Wu SC conceived and designed the study and wrote the initial draft of the manuscript; Chen WT participated in study design and conception; Muo CH performed the data analysis and interpretation and was involved in writing the initial draft of manuscript; Wu SC and Hsu CY performed data analysis and interpretation as well as manuscript drafting and revision. Guarantor of the article: Shih-Chi Wu, MD, PhD.

Funding Information

This study is supported in part by the Ministry of Health and Welfare, Taiwan (MOHW107-TDU-B-212-123004), China Medical University Hospital (DMR-107-192), Academia Sinica Stroke Biosignature Project (BM10701010021), MOST Clinical Trial Consortium for Stroke (MOST 106-2321-B-039-005), Tseng-Lien Lin Foundation, Taichung, Taiwan, and Katsuzo and Kiyo Aoshima Memorial Funds, Japan.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflicts of interest.

Ethics Approval and Consent to Participate

For complying with the Personal Information Protection Act, the data abstracted from the chart contained no identification of patient information. All identifications of patients were replaced with surrogate numbers for research uses. This study was approved by the Research Ethics Committee at China Medical University and Hospital (CMUH106-REC3-085).

Supplementary material

11605_2019_4442_MOESM1_ESM.docx (26 kb)
ESM 1 (DOCX 25 kb)


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Copyright information

© The Society for Surgery of the Alimentary Tract 2019

Authors and Affiliations

  1. 1.Graduate Institute of Clinical Medical ScienceChina Medical UniversityTaichungTaiwan
  2. 2.Trauma and Emergency CenterChina Medical University HospitalTaichungRepublic of China
  3. 3.Department of SurgeryChina Medical University HospitalTaichungTaiwan
  4. 4.Management Office for Health DataChina Medical University and HospitalTaichungTaiwan

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